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rs1801260

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004898.4(CLOCK):c.*213T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 587,320 control chromosomes in the GnomAD database, including 21,892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4961 hom., cov: 32)
Exomes 𝑓: 0.27 ( 16931 hom. )

Consequence

CLOCK
NM_004898.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.802
Variant links:
Genes affected
CLOCK (HGNC:2082): (clock circadian regulator) The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
TMEM165 (HGNC:30760): (transmembrane protein 165) This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLOCKNM_004898.4 linkuse as main transcriptc.*213T>C 3_prime_UTR_variant 23/23 ENST00000513440.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLOCKENST00000513440.6 linkuse as main transcriptc.*213T>C 3_prime_UTR_variant 23/231 NM_004898.4 P1

Frequencies

GnomAD3 genomes
AF:
0.246
AC:
37470
AN:
152032
Hom.:
4955
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.172
Gnomad AMI
AF:
0.270
Gnomad AMR
AF:
0.233
Gnomad ASJ
AF:
0.236
Gnomad EAS
AF:
0.0993
Gnomad SAS
AF:
0.370
Gnomad FIN
AF:
0.356
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.280
Gnomad OTH
AF:
0.246
GnomAD4 exome
AF:
0.272
AC:
118169
AN:
435170
Hom.:
16931
Cov.:
4
AF XY:
0.278
AC XY:
63693
AN XY:
229406
show subpopulations
Gnomad4 AFR exome
AF:
0.179
Gnomad4 AMR exome
AF:
0.218
Gnomad4 ASJ exome
AF:
0.231
Gnomad4 EAS exome
AF:
0.130
Gnomad4 SAS exome
AF:
0.359
Gnomad4 FIN exome
AF:
0.339
Gnomad4 NFE exome
AF:
0.276
Gnomad4 OTH exome
AF:
0.260
GnomAD4 genome
AF:
0.246
AC:
37495
AN:
152150
Hom.:
4961
Cov.:
32
AF XY:
0.252
AC XY:
18704
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.172
Gnomad4 AMR
AF:
0.234
Gnomad4 ASJ
AF:
0.236
Gnomad4 EAS
AF:
0.0991
Gnomad4 SAS
AF:
0.371
Gnomad4 FIN
AF:
0.356
Gnomad4 NFE
AF:
0.280
Gnomad4 OTH
AF:
0.245
Alfa
AF:
0.268
Hom.:
9691
Bravo
AF:
0.226
Asia WGS
AF:
0.261
AC:
908
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
9.3
Dann
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1801260; hg19: chr4-56301369; COSMIC: COSV59401751; API